People

Faculty

Podbilewicz Benjamin , Professor

Research Interests

We
are using the nematode Caenorhabditis
elegans to
investigate cell fusion, organ formation, and nerve cell development.
The wealth of anatomical, genetic, developmental, and molecular
information available for C.
elegans
provides a multidisciplinary and powerful approach for these studies.
Our work has focused on the study of one fundamental biological
question: How
do cells fuse?
Cells fuse during fertilization and formation of organs. For example,
macrophages, eye lens cells, placental cells, and muscle human cells
fuse. We also work on how cells migrate, change shapes, and sculpt
organs and how cell fusion and organ formation evolve.We initially
approached cell fusion by mutational analysis, obtaining many
mutations in two genes that we found are critical for the cell fusion
process. We identified EFF-1 and AFF-1, two type I membrane proteins
essential and sufficient for developmental cell fusion in C.
elegans.
EFF-1 and AFF-1 are the founders of the first family of eukaryotic
cell fusion proteins (fusogens). EFF-1 and AFF-1 from nematodes can
fuse heterologous insect cells. EFF-1 is required in both fusing
cells and the process is via hemifusion. We will purify and determine
the three-dimensional structure of EFF-1 and AFF-1 proteins, we will
test their fusogenic activities in cells and in reconstituted
liposomes. Our ultimate goal is to understand the molecular and
physicochemical mechanisms of cell membrane fusion.We have
accomplished a complete description of the cellular events leading to
the formation of an organ. Using genetic analyses we identify genes
that function to control different cell fusion events in C.
elegans and
in other organisms and how this process is regulated in development.
Homotypic cell-cell fusion may control the size of syncytia by
preventing fusion with neighboring cells. We now focus on
fertilization, the development of vulva, epidermis, muscles and
pharynx.

Pruning of neuronal trees.
We
discovered that EFF-1 is also required to sculpt complex neuronal
trees required for sensing strong mechanical stimuli. We found that
EFF-1 trims abnormal or excessive neuronal branches as a novel
quality control mechanism. EFF-1 works in specific neurons by fusing
excess and abnormal branched neuronal branches. In additional EFF-1
retracts branches. We have identified other genes that participate in
the generation and maintenance of complex neuronal trees and we hope
that our discoveries in C.
elegans may
help to understand and repair degenerative diseases of the nervous
system and accidental breaking of neurons.

Evolution of organogenesis.
We study
cellular events during morphogenesis of the vulva across species. We
found that changes in the direction of cell divisions can result in
differences in size and shape of the vulva. We found that evolution
of most vulval characters are biased and proposed that evolution of
the vulva in nematodes is governed by selection and/or
selection-independent constraints and not by stochastic processes. We
are also trying to find missing fusion proteins that act in
fertilization and muscle formation in worms and mammals.